Jivani R R, Patel C N, Jivani N P
Department of Pharmaceutics, C. U. Shah College of Pharmacy and Research, Wadhwan-363 030, India.
Indian J Pharm Sci. 2012 Jul;74(4):302-11. doi: 10.4103/0250-474X.107049.
The current study involves the fabrication of oral bioadhesive bilayer matrices of narrow absorption window drug baclofen and the optimisation of their in vitro drug release and characterisation. Statistical design of experiments, a computer-aided optimisation technique, was used to identify critical factors, their interactions and ideal process conditions that accomplish the targeted response(s). A central composite design was employed to systematically optimise the drug delivery containing a polymer, filler and compression force. The values of ratio of different grades of hydroxypropyl methylcellulose, microcrystalline cellulose and compression force were varied to be fitted in design. Drug release at 1 h (Q1), 4 h (Q4), 8 h (Q8), 12 h (Q12), and hardness were taken as responses. Tablets were prepared by direct compression methods. The compressed tablets were evaluated for their hardness, weight variation, friability, content uniformity and diameter. Counter plots were drawn and optimum formulation was selected by desirability function. The formulations were checked for their ex vivo mucoadhesion. The experimental value of Q1, Q4, Q8, Q12 and hardness for check-point batch was found to be 31.64, 45.82, 73.27, 98.95% and 4.4 kg/cm(2), respectively. The release profile indicates Highuchi kinetics (Fickian transport) mechanism. The results of the statistical analysis of the data demonstrated significant interactions amongst the formulation variables, and the desirability function was demonstrated to be a powerful tool to predict the optimal formulation for the bilayer tablet.
本研究涉及窄吸收窗药物巴氯芬口腔生物黏附双层基质的制备及其体外药物释放的优化与表征。采用实验的统计设计这一计算机辅助优化技术，以确定关键因素、它们之间的相互作用以及实现目标响应的理想工艺条件。采用中心复合设计来系统优化包含聚合物、填充剂和压片力的药物递送体系。改变不同等级羟丙基甲基纤维素、微晶纤维素的比例值以及压片力，以符合设计要求。将1小时（Q1）、4小时（Q4）、8小时（Q8）、12小时（Q12）的药物释放量以及硬度作为响应指标。通过直接压片法制备片剂。对压制片剂的硬度、重量差异、脆碎度、含量均匀度和直径进行评价。绘制等高线图，并通过期望函数选择最佳配方。检查配方的体外黏膜黏附性。发现检查点批次的Q1、Q4、Q8、Q12和硬度的实验值分别为31.64%、45.82%、73.27%、98.95%和4.4 kg/cm²。释放曲线表明符合 Higuchi 动力学（菲克扩散）机制。数据的统计分析结果表明配方变量之间存在显著相互作用，期望函数被证明是预测双层片剂最佳配方的有力工具。
